Human skin is made up of two main layers, namely the dermis and the epidermis that superficially covers the dermis. Natural human epidermis is composed mainly of three types of cells, namely keratinocytes, which form the vast majority, melanocytes and Langerhans cells. Each of these three types of cells contributes, via its intrinsic functions, to the essential role played in the body by the skin, especially the role of protecting the body against external attacking factors (the climate, ultraviolet rays, tobacco, etc.), which is also known as the “barrier function”.
The epidermis is a keratinized, stratified pavement epithelium 90% formed from keratinocytes. The gradual differentiation of the cells of the basal membrane, which separates the dermis from the epidermis, towards the surface of the epidermis especially includes the differentiation of keratinocytes, which migrate towards the surface of the skin, where they desquamate.
Ageing of the epidermis is manifested mainly by a reduction in its thickness. Atrophy of the epidermis is the consequence of the slowing down of keratinocyte proliferation and of the accumulation of senescent keratinocytes. The horny layer becomes dull.
The dermis provides the epidermis with a solid support. It is also its nourishing element. It is made up mainly of fibroblasts and an extracellular matrix composed mainly of collagen, elastin and a substance known as ground substance. These components are synthesized by the fibroblasts. The cohesion between the epidermis and the dermis is provided by the dermo-epidermal junction. This is a complex region about 100 nm thick, which comprises the basal pole of the basal keratinocytes, the epidermal membrane and the sub-basal zone of the superficial dermis.
Collagens are the major proteins of the extracellular matrices of the skin. To date, 20 types of collagen have been identified, and are noted from I to XX. The collagens predominantly present throughout the epidermis are collagens of the type I and III that form the extracellular matrix of the entire dermis (these collagens constitute 70-80% of the dry weight of the dermis). Moreover, collagens are not all synthesized by the same cell types: collagens of type I and III are essentially produced by the dermal fibroblasts, whereas type VII collagen is produced by two categories of cell, keratinocytes and fibroblasts. Regulation of their expression differs from one collagen to another, for example collagens I and VII are not regulated in the same way by certain cytokines; specifically, TNF-α and leukoregulin stimulate collagen VII and negatively regulate collagen I. Finally, all collagen molecules are variants of a common precursor, which is the α chain of procollagen.
With age, collagen becomes thinner and wrinkles appear on the surface of the skin. Cutaneous ageing is a genetically programmed mechanism.
Moreover, certain environmental factors such as smoking and exposure to sunlight accelerate it. The skin thus has a much more aged appearance on the areas exposed to sunlight, such as the back of the hands or the face. Thus, these other factors also have a negative impact on the natural collagen of the skin.
Consequently, given the important role of collagen in the integrity of the skin and in its resistance to external attacking factors of mechanical type, stimulation of the synthesis of these collagens, and in particular of type I collagen, appears to be an effective means for overcoming the signs of ageing of the skin. During chronological ageing, the epidermis also undergoes many modifications and degradations that are reflected, with age, by an impairment in the microrelief, associated with an impairment in the barrier function of the skin, the appearance of wrinkles and fine lines, an impairment in the mechanical properties of the skin, especially lack of elasticity of the skin, and loss of radiance of the complexion.
The importance of having available products whose effects are directed towards regenerating skin tissue via increasing keratinocyte proliferation and stimulating fibroblast proliferation and/or metabolism, and especially stimulating collagen synthesis, may thus be appreciated.
It is known practice from the literature to use agents such as retinol, which promote keratinocyte proliferation and can stimulate epidermal renewal and maintain and/or increase the thickness of the epidermis: this is then referred to as a direct biological effect. However, retinol has a certain number of drawbacks when it is used in a cosmetic composition. Specifically, it has low stability towards oxidation and gives rise to adverse side effects on consumers, especially such as skin irritation. There is thus a need to find other compounds with a direct biological effect, which are readily available and whose efficacy is acceptable for optimal use in cosmetics.